title: Prevention of type 2 diabetes in subjects with prediabetes and metabolic syndrome treated with phentermine and topiramate extended release.
abstract: OBJECTIVE To evaluate over 108 weeks the effect of phentermine and topiramate extended release (PHEN/TPM ER) treatment on progression to type 2 diabetes and/or cardiometabolic disease in subjects with prediabetes and/or metabolic syndrome (MetS) at baseline. RESEARCH DESIGN AND METHODS Subanalysis of a phase 3, randomized, placebo-controlled, double-blind study of overweight/obese subjects (BMI ≥27 to ≤45 kg/m(2)) with two or more comorbidities. Subjects were randomized to placebo, PHEN 7.5 mg/TPM ER 46 mg (7.5/46), or PHEN 15 mg/TPM ER 92 mg (15/92) plus lifestyle modifications for 108 weeks. Percent weight loss in the intent-to-treat population using multiple imputation (ITT-MI), annualized incidence rate of progression to type 2 diabetes, and changes in glycemia, lipid parameters, blood pressure, and waist circumference were evaluated. RESULTS At baseline, 475 subjects met the criteria for prediabetes and/or MetS. After 108 weeks, subjects with prediabetes and/or MetS in the placebo, 7.5/46, and 15/92 groups experienced mean percent weight loss of 2.5, 10.9, and 12.1%, respectively (ITT-MI; P < 0.0001 vs. placebo), associated with reductions of 70.5 and 78.7% in the annualized incidence rate of type 2 diabetes for those receiving 7.5/46 and 15/92, respectively (ITT, P < 0.05), versus placebo. The ability of PHEN/TPM ER to prevent diabetes was related to degree of weight lost and was accompanied by significant improvements in cardiometabolic parameters. PHEN/TPM ER was well tolerated by this subgroup over 2 years. CONCLUSIONS PHEN/TPM ER plus lifestyle modification produced significant weight loss and markedly reduced progression to type 2 diabetes in overweight/obese patients with prediabetes and/or MetS, accompanied by improvements in multiple cardiometabolic disease risk factors.
authors.affiliation: Corresponding author: W. Timothy Garvey, garveyt@uab.edu.
authors.forename: W Timothy
authors.initials: WT
authors.lastname: Garvey
authors.forename: Donna H
authors.initials: DH
authors.lastname: Ryan
authors.forename: Robert
authors.initials: R
authors.lastname: Henry
authors.forename: Nancy J V
authors.initials: NJ
authors.lastname: Bohannon
authors.forename: Hermann
authors.initials: H
authors.lastname: Toplak
authors.forename: Michael
authors.initials: M
authors.lastname: Schwiers
authors.forename: Barbara
authors.initials: B
authors.lastname: Troupin
authors.forename: Wesley W
authors.initials: WW
authors.lastname: Day
mesh_terms: D019440:Anti-Obesity Agents / Q000008:administration & dosage / Q000627:therapeutic use; D003692:Delayed-Action Preparations; D003924:Diabetes Mellitus, Type 2 / Q000517:prevention & control*; D005260:Female; D005632:Fructose / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006801:Humans; D008019:Life Style; D008297:Male; D024821:Metabolic Syndrome / Q000150:complications / Q000188:drug therapy*; D008875:Middle Aged; D010645:Phentermine / Q000008:administration & dosage / Q000627:therapeutic use*; D010919:Placebos; D011236:Prediabetic State / Q000150:complications / Q000188:drug therapy*; D000077236:Topiramate
chemical_list: D019440:Anti-Obesity Agents; D003692:Delayed-Action Preparations; D010919:Placebos; D000077236:Topiramate; D005632:Fructose; D010645:Phentermine